Overall cognitive profiles in patients with GLUT1 Deficiency Syndrome

Abstract

Introduction Glucose Transporter Type I Deficiency Syndrome ( GLUT 1 DS ) classical symptoms are seizures, involuntary movements, and cognitive impairment but so far the literature has not devoted much attention to the last. Methods In our retrospective study involving 25 patients with established GLUT 1 DS diagnosis, we describe the cognitive impairment of these patients in detail and their response to the ketogenic diet in terms of cognitive improvement. Results We outlined a specific cognitive profile where performance skills were more affected than verbal ones, with prominent deficiencies in visuospatial and visuomotor abilities. We demonstrated the efficacy of ketogenic diet ( KD ) on cognitive outcome, with particular improvement tin total and verbal IQ ; we found that timing of KD introduction was inversely related to IQ outcome: the later the starting of KD , the lower the IQ , more notable nonverbal scale (verbal IQ correlation coefficient −0.634, p ‐value = 0.015). We found a significant direct correlation between cognition and CSF /blood glucose ratio values: the higher the ratio, the better the cognitive improvement in response to diet (from T0–baseline evaluation to T1 on average 18 months after introduction of KD ‐: TIQ correlation coefficient 0.592, p ‐value = 0.26; VIQ correlation coefficient 0.555, p ‐value = 0.039). Finally, we demonstrated that a longer duration of treatment is necessary to find an improvement in patients with “severely low ratio.” Conclusion Our results were consistent with the hypothesis that timing of the diet introduction is a predictive factor of cognitive outcome in these patients, confirming that earlier initiation of the diet may prevent the onset of all GLUT 1 DS symptoms: epilepsy, movement disorders, and cognitive impairment.

Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group

“…Performance skills usually are more affected than verbal skills, with prominent deficiencies in visuospatial and visuomotor abilities. Timing of KDT introduction is a predictive factor for cognitive outcome 29,34 . Early dietary treatment correlates with better intellectual and social adaptive skills 25 …”

“…Ineffective seizure control in Glut1DS despite KDT has been reported 29,61 . Movement disorders and cognitive issues also improve with dietary KDT 25,29,34,47 . The general management of KDT for drug‐resistant childhood epilepsy and for Glut1DS is described in the revised international consensus 8 .…”

“…Follow‐up needs to be age‐specific as symptoms change from primarily seizures in infancy‐early childhood to movement disorders such as dystonia and paroxysmal exertional dyskinesias in adolescence‐adulthood 25 . Cognitive dysfunction persists throughout life but there is no evidence for progressive worsening 34 . Long‐term adverse effects of KDT such as growth impairment, nephrolithiasis, and cardiovascular risks need to be monitored at regular intervals 8 …”

The effect of chronic neuroglycopenia on resting state networks in GLUT1 syndrome across the lifespan

“…Putamen seeds positively correlate with associative frontal regions implicated in executive function control reproducing the FC of the rostral putamen division observed in controls (Di Martino et al, ). Executive functions and attention impairment have been reported in GLUT1DS (De Giorgis et al, ; Ragona et al, ).…”

Metabolic Disorders Presenting with Seizures in the Neonatal Period

“…In support, a retrospective case series described improvements in total IQ and verbal IQ scores at 18-and 36-month follow-up after initiation of the ketogenic diet. 51 Optimal long-term outcomes are achieved in those with early introduction of the diet, preferably within the first year of life. 52 Triheptanoin, a triglyceride containing three C7:0 fatty acids, is a candidate therapy for GLUT1 deficiency.…”